This proposal requests five years of continued support for the Mayo General Clinical Research Center, now in its eighteenth year of operation. The last five years have been productive as evidenced by the increase in publications related to work performed at the GCRC. During this period there has been a significant increase in outpatient studies and visits. This will continue during the next 5 years and we project more than 6000 outpatient visits in the twenty-five year of the grant. With increased outpatient activity there was initially a concomitant fall in inpatient activity; however, over the last two years, there has been a gradual increase in inpatient studies. We project more than 2000 inpatient bed- days in the twenty-first year of the grant. Other changes that have occurred during the last grant period include an increase in short labor- intensive studies, an increase in studies with more acutely ill patients and an increase in usage of the unit by new disciplines and investigations. These trends will continue during the next five years with the development of major programs in hypertension, ophthalmology, and oncology. During this grant period, there was a dramatic expansion in the use of computers in clinical research at the GCRC resulting in the growth of Mayo supported Research Computer Facility. In the next 5 years, we are planning for major changes and continue expansion in our computer resources with implementation of improved hardware (e.g., Unix workstations) and software (e.g., PROPHET and INGRES). The migration from the present system to this new environment will require significant program support. Recently, the CRC Advisory Committee has expanded its role of reviewing protocols, setting priorities, and establishing policies while working very closely with the program director to assure that studies done at the GCRC are of the highest quality. This expanded role of the Advisory Committee will continue during the next 5 years. The established protocol review process ensures appropriate and expert scientific and statistical review early during protocol development. The major on-going programs now using the resources of the Mayo GCRC include: diabetes mellitus, metabolic bone disease, calcium metabolism, lipolysis, surgical and medical gastroenterology, and cardiovascular disease. New growing programs that will be important components of the Mayo GCRC during the next 5 years include: studies of ciliary body function and aqueous humor formation by the Department of Ophthalmology; phase I, phase II, and pharmacology studies of anticancer agents by the Department of Oncology; and studies of hypertension. This core of major users is predominantly extramurally funded, with a spectrum of investigators from new, young individuals to more experienced principle investigators.